A once-a-month electronic newsletter for basic, preclinical and translational research news related to the Johns Hopkins School of Medicine. Please forward freely. Find back issues at http://www.hopkinsmedicine.org/mediaII/ScienceNewsletter/index.html
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RESEARCH HIGHLIGHTS:
+ Junk DNA May Not Be So Junky After All
+ Picking Apart How Neurons Learn
+ Researchers Identify Genes in Fruit Flies That May Shed Light on Human Cancer Spread
+ New Gene Reduces Retinal Degeneration in Fruit Flies
+ Lizard “Third Eye” Sheds Light on Evolution of Color Vision
+ Whole-Genome Study at Johns Hopkins Reveals a New Gene Associated With Abnormal Heart Rhythm
NEWS BRIEFS:
+ 3rd Dintzis Lecture: “Structure and Action of Chaperones for Protein Folding”
Wayne A. Hendrickson, Ph.D. 4 p.m., Wednesday, May 3, 2006
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Do you have an interesting research finding about one month from publication or presentation? Fax your manuscript or galley proofs to Media Relations and Public Affairs at 410-614-8951, or email the appropriate media relations person online at
http://www.hopkinsmedicine.org/mediaII/Staff/index.html
For more info on a story, click the accompanying hyperlink. Please note: Some Internet links may not appear on a single line. If a hyperlink fails, check for continuation of the address on the next line.
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RESEARCH HIGHLIGHTS:
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3/23/06
Junk DNA May Not Be So Junky After All
Researchers at the McKusick-Nathans Institute of Genetic Medicine have invented a cost-effective and highly efficient way of analyzing what many have termed “junk” DNA and identified regions critical for controlling gene function.
The researchers developed a new system that uses zebrafish to test mammalian DNA and identify DNA sequences, known as enhancers, involved in turning on a gene. In studying RET, the major gene implicated in Hirschsprung disease and multiple endocrine neoplasia (MEN2), the team identified DNA sequences that can control RET but had not been identified using standard methods. Hirschsprung disease, also known as congenital megacolon, is a relatively common birth defect marked by bowel obstruction. MEN2 is an inherited predisposition to neuroendocrine cancers.
The researchers’ next steps are further study of the RET enhancers they found to identify other mutations that might contribute to Hirschsprung disease and MEN2, and to entice other investigators to collectively build a database of human enhancers. “If there’s one thing we’ve learned here, it’s that we are not very good at recognizing enhancers. We just don’t know what they look like,” says Fisher. “We are anxious for others to use this technology on their favorite genes.” http://www.hopkinsmedicine.org/Press_releases/2006/03_23_06.html
Science (Published online March 23, 2006)http://www.sciencemag.org/cgi/content/abstract/1124070v1
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3/29/06
Picking Apart How Neurons Learn
Johns Hopkins researchers have used mouse mutants to define critical steps involved in learning basic motor skills. The study focuses on the behavior of two proteins and the specific steps they take to control a neuron’s ability to learn by adapting to signals from other nerve cells. Published in the March 16 issue of Neuron, the study shows definitively that interactions between the PICK1 protein and AMPA receptors are critical Purkinje cells in the brain to become de-sensitized to certain molecular signals.
Desensitization to signals from neighboring neurons – a process known as long-term depression, or LTD – is thought to be responsible for several forms of motor learning, including the vestibulo-ocular reflex, which coordinates eye movements with head movements, allowing us to perform activities such as reading in a moving automobile.
Mice lacking the PICK1 protein are unable to establish LTD or remove AMPA receptors from cell surfaces. When PICK1 is added artificially back into these neurons, AMPA receptors are removed and LTD is restored, showing that PICK1 is necessary for LTD. Mice lacking the part of the AMPA receptor thought to physically interact with PICK1 also do not establish LTD. This result confirms that PICK1 must physically touch the AMPA receptor for LTD to occur.
With three different mutant mouse populations in hand, the research team is poised to further dissect the molecular mechanisms behind learning. “The next step is to determine whether LTD is crucial for motor learning, the so-called holy grail in the field,” says one of the study’s co-first authors, Jordan Steinberg, an M.D., Ph.D. candidate at Hopkins. http://www.hopkinsmedicine.org/Press_releases/2006/03_29_06.html
Neuron, Vol 49, 845-860, March 16, 2006
http://www.neuron.org/content/article/abstract?uid=PIIS0896627306001681
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4/3/06
Researchers Identify Genes in Fruit Flies That May Shed Light on Human Cancer Spread
By searching through all the genes in the fruitfly genome using a DNA microarray, Johns Hopkins scientists have identified 353 genes that are preferentially turned on in so-called border cells of the fruitfly ovary that migrate during normal development. Two main types of genes came out of this search: those known to be involved in maintaining cell shape and structure and which become very dynamic in migrating cells; and a group of genes involved in transporting materials from the inside of a cell to its membrane surface and back again.
Published April 3 in Developmental Cell, the study has implications for understanding cell migration and perhaps controlling cancer cells that move similarly to spread beyond an original tumor, which are what eventually kills most cancer patients.
Some of the genes found are known to play a role in both border cell migration in fruitflies and metastasis in animal cancer cells; some that had long been suspected to play a role in cell migration, but have been more difficult to study because their functions are shared by other genes; and some that are well understood for their roles in other cellular functions but without this study would not have been obvious candidate genes in cell migration. The results help these researchers as well as others in the field by pointing out genes to study further.
“This really was a hypothesis-generating experiment,” says Montell. “The results of this study tell us where to focus future efforts.” http://www.hopkinsmedicine.org/Press_releases/2006/04_03_06.html
Developmental Cell, Vol 10, 483-495, April 2006
http://www.developmentalcell.com/content/article/abstract?uid=PIIS1534580706000645
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4/13/06
New Gene Reduces Retinal Degeneration in Fruit Flies
In teasing apart the molecular interactions and physiology underlying light perception, Johns Hopkins researchers have discovered a gene in fruit flies that helps certain specialized neurons respond more quickly to bright light and dubbed the gene “Lazaro.” They found that this gene is required for a second biochemical pathway that controls the activity of a protein called the TRP channel. The fly TRP channel is the founding member of a family of related proteins in mammals that are essential for guiding certain nerves during development and for responding to stimuli including light, heat, taste and sound. The study was published in the April 4 issue of Current Biology.
By shining bright light onto and recording electrical changes in single nerve cells in the fly eye, researchers found that neurons carrying a mutation in this gene cannot respond as well to light as compared to neurons carrying normal copies of this gene. In fact, the mutant neurons turn off their response to light four times faster than normal neurons. Because Lazaro helps fly TRP channels work at their maximum, it is possible that a Lazaro-like gene in mammals might also play a role in how well mammalian TRP channels work.
“These results have implications for understanding sensory signaling in mammals,” says the study’s senior author, Craig Montell, Ph.D., a professor in the biological chemistry department in the Institute of Basic Biomedical Sciences at Hopkins. http://www.hopkinsmedicine.org/Press_releases/2006/04_14a_06.html
Current Biology, Vol 16, 723-729, 4 April 2006 http://www.current-biology.com/content/article/abstract?uid=PIIS0960982206012073
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4/13/06
Lizard “Third Eye” Sheds Light on Evolution of Color Vision
Lizards have given Johns Hopkins researchers a tantalizing clue to the evolutionary origins of light-sensing cells in people and other species. Published in the March 17 issue of Science, their lizard study describes how the “side-blotched” lizard’s so-called third, or parietal, eye, distinguishes two different colors, blue and green, possibly to tell the time of day. Specialized nerve cells in that eye, which looks more like a spot on the lizard’s forehead, use two types of molecular signals to sense light: those found only in simpler animals, like scallops, and those found only in more complex animals like humans.
According to the researchers, when the lizard’s third eye sees blue light, the blue pigment triggers a molecule called gustducin, which is very similar to a molecule found in human photoreceptors as well as the lateral eyes of the lizard – those on the sides of its head. But when the lizard’s third eye sees green light, the green pigment triggers a different molecule called Go, known as “G-other,” which also signals light responses in the light-sensing cells of the scallop and other creatures without a backbone. That Go is found in spineless creatures suggests it is the evolutionarily more ancient light-triggering signal.
Although gustducin and Go are different molecules, they are similar and considered “related” proteins. However, gustducin and Go each activate different molecular pathways that work against each other physiologically. “Incorporating two different pigments and two separate signaling molecules in one cell may have been an economical way, in a primitive eye with relatively few cell types, to tell the transitions of the day based on changes in the spectrum of sunlight,” says Chih-Ying Su, Ph.D., the first author of the study and a former neuroscience graduate student at Hopkins. http://www.hopkinsmedicine.org/Press_releases/2006/04_14_06.html
Science 17 March 2006: Vol. 311. no. 5767, pp. 1617 - 1621 http://www.sciencemag.org/cgi/content/abstract/311/5767/1617
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4/26/06
Whole-Genome Study at Johns Hopkins Reveals a New Gene Associated With Abnormal Heart Rhythm
Using a new genomic strategy that has the power to survey the entire human genome and identify genes with common variants that contribute to complex diseases, researchers at Johns Hopkins have identified a gene that may predispose some people to abnormal heart rhythms that lead to sudden cardiac death, a condition affecting more than 300 thousand Americans each year. The gene called NOS1AP, not previously flagged by or suspected from more traditional gene-hunting approaches, appears to influence significantly one particular risk factor – the so-called QT interval length – for sudden cardiac death. The work was published online at Nature Genetics on April 30.
QT interval measures the period of time it takes the heart to recover from the ventricular beat – when the two bottom chambers of the heart pump. Corresponding to the “lub” part of the “lub-dub” pattern of the heartbeat, an individual’s QT interval remains constant. This interval is partly dependent on one’s genetic constitution and, moreover, genes also play a role in sudden cardiac death.
The team first focused on people who have extremely long or short QT intervals and used subjects from two population-based studies, about 1800 American adults of European ancestry from the Framingham Heart Study of Framingham, Mass., and about 6,700 German adults from the KORA-gen study of Augsburg, Germany and searched for any specific DNA sequences that appear more frequently in people who have longer or shorter QT intervals than in those with normal QT intervals.
Only one particular single nucleotide polymorphism, known as a SNP – found near the NOS1AP gene – correlated with QT interval. Not previously suspected to play a role in heart function, the NOS1AP gene is turned on in the left ventricle of the human heart and is active in the right place and time to play a role in QT interval. http://www.hopkinsmedicine.org/Press_releases/2006/04_30_06.html
Nature Genetics advanced online publication April 30, 2006 http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng1790.html
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NEWS BRIEFS:
3rd Dintzis Lecture: Structure and Action of Chaperones for Protein Folding
4 p.m., Wednesday, May 3, 2006 -- Wood Basic Science Auditorium
The Department of Biophysics and Biophysical Chemistry in the Institute of Basic Biomedical Sciences at Johns Hopkins presents the third Dintzis Lecture honoring the department’s first chairman, Howard Dintzis, Ph.D. The lecture series aims to highlight successful research in structural and molecular biology.
This year’s lecture will be presented by Wayne A. Hendrickson of the Howard Hughes Medical Institute and Columbia University in New York. Hendrickson has been a world leader in the development and application of diffraction methods for the study of macromolecular structure. His work has had a profound impact on virtually all aspects of molecular biology and led to particularly important insights into the mechanism of HIV infection. The topic of Hendrickson’s lecture will be the structure and mechanism of chaperone proteins, which are essential to aid the proper folding and function of many key proteins. All are welcome, no registration required.
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-- JHM --
